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Focused Issue of This Month Drug Therapy and Catheter Ablation for Atrial Fibrillation Young Hoon Kim, MD. Division of Cardiology, Korea University College of Medicine Email : yhkmd@korea.ac.kr J Korean Med Assoc 2008; 51(4): 317-326 Abstract In all clinical trials comparing rate versus rhythm control of atrial fibrillation (AF) by drugs, there was no survival benefit associated with a rhythm control strategy. Currently used antiarrhythmic drugs are not only frequently ineffective at eliminating AF, but may be life threatening in some patients. Catheter ablation (CA) of AF has evolved rapidly and has become accepted as one of the therapeutic modalities for controlling AF. The effective strategies for CA of AF consist of pulmonary vein isolation (PVI) and/or complete encirclement around PVs with or without additional ablation lines. Selection of patients, who may be benefited by CA or not, is an important issue. Precise electroanatomic mapping for the triggers and the substrate of the atria is central for customizing ablation target and for enhancing efficacy of CA for AF. With further development of new energy sources of ablation, cardiac imaging, navigation, and mapping systems, the CA can be simplified and standardized, which may enable the CA to become more effective, safer, and more applicable to many different subsets of AF. Keywords : Atrial fibrillation; Catheter ablation; Antiarrhythmic drugs; Mapping 317

Kim YH Amio=amiodarone, Cath=catheter, Dofet=dofetilide, LVH=left ventricular hypertrophy Figure 1. Selection of antiarrhythmic drugs for the maintenance of sinus rhythm. ACC/AHA/ESC Practice Guidelines 2006. 318

Drug Therapy and Catheter Ablation for Atrial Fibrillation I avf V1 L1,2 L2,3 L3,4 L4,5 L5,6 L6,7 L7,8 L8,9 L9,10 ABL d ABL p PVP (*) elimination and dissociated during RF application RF=radiofrequency Figure 2. Dissociated pulmonary vein potential (PVP, *) from the let atrium after ablation. 319

Kim YH 250 200 150 100 50 PeAF PAF Freedom form AF recurrence (%) 100 75 50 25 P=0.061 Paroxysmal AF Persistent AF 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 0 10 20 30 PAF=paroxysmal AF, PeAF=persistent AF Figure 3. Number of catheter ablation of atrial fibrillation at Korea University Medical Center (KUMC, 1998~2007, n=680). 0 Figure 4. Longterm freedom from AF recurrence in patients with paroxysmal AF and persistent AF at KUMC (n=533). 320

Drug Therapy and Catheter Ablation for Atrial Fibrillation Selective PV lsolation vs. Empirical Fcur PVs lsolation SePVI EmPVI A B Figure 5. Selective arrhythmogenic pulmonary vein isolation (A) and empirical 4 pulmonary veins isolation (B). Pak HN, et al. J Cardiovasc Electrophysiol 2008 (In press). Cumulative AF Recurrence Rate AF Free Rate 1.0 % 30 0.8 25 0.6 15 0.4 10 0.2 5 0.0 0 0 10 20 30 40 50 29.723.1 months of Follow Up Time (months) 60 70 Figure 6. Atrial fibrillation recurrence rate after selective arrhythmogenic pulmonary vein isolation (SePVI) and empirical 4 pulmonary veins isolation (EmPVI). Pak HN, et al. J Cardiovasc Electrophysiol 2008 (In press). AF Free Rate (%) 321

Kim YH Figure 7. Automated map of complex fractionated atrial electrograms (CFAEs) during atrial fibrillation (6 seconds segment). The areas of white and red color illustrate CFAE with cycle length <80ms and <120ms, respectively. 322

Drug Therapy and Catheter Ablation for Atrial Fibrillation Before ablation After ablation Figure 8. Linear ablation along the complex fractionated atrial electrograms (CFAEs, white color denotes cycle length <120ms) during atrial fibrillation. Panel A shows automated CFAE map at baseline and panel B shows the summary of ablation of the antra of 4 pulmonary veins and linear extension to the areas showing CFAE. A B 323

Kim YH 10mV 5mV 0mV RSPV RIPV Anterior view LSPV POST VMPP Voltage Map Figure 9. Voltage map after isolation of 4 pulmonary veins and linear ablation at the roof and perimitral isthmus in patients with chronic, persistent atrial fibrillation. The voltage of the areas within the ablation lines convert to less than 0.2mV defining as gray color. LAA Line at the perimitral isthmus LSPV Posterior view roof line LIPV RSPV RIPV 324

Drug Therapy and Catheter Ablation for Atrial Fibrillation 11. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD. Atrial Fibrillation Followup Investigation of Rhythm Management (AFFIRM). Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-1833. 12. Hal ssaguerre M, Jal s P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Me tayer P, Cle - menty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659-666. 13. Pak HN, Hwang C, Lim HE, Kim JW, Lee HS, Kim YH. Electroanatomic characteristics of atrial premature beats triggering atrial fibrillation in patients with persistent versus paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2006; 17: 818-824. 14. Rha SW, Kim YH, Hong MK, Ro YM, Choi CU, Suh SY, Kim JW, Kim EJ, Park CG, Seo HS, Oh DJ. Mechanisms responsible for the initiation and maintenance of atrial fibrillation assessed by noncontact mapping system. Int J Cardiol 2008; 124: 218-226. 15. Hal ssaguerre M, Jal s P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Roudaut R, Cle menty J. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000; 101: 1409-1417. 16. Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, AbdulKarim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol 2002; 40: 464-474. 17. Oral H, Knight BP, Tada H, Ozaydin M, Chugh A, Hassan S, Scharf C, Lai SW, Greenstein R, Pelosi F Jr, Strickberger SA, Morady F. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation 2002; 105: 1077-1081. 18. Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, Salvati A, Dicandia C, CalabròMP, Mazzone P, Ficarra E, Di Gioia C, Gulletta S, Nardi S, Santinelli V, Benussi S, Alfieri O. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 2001; 104: 2539-2544. 19. Oral H, Scharf C, Chugh A, Hall B, Cheung P, Good E, Veerareddy S, Pelosi F Jr, Morady F. Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 2003; 108: 2355-2360. 10. Kottkamp H, Tanner H, Kobza R, Schirdewahn P, Dorszewski A, GerdsLi JH, Carbucicchio C, Piorkowski C, Hindricks G. Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure? J Am Coll Cardiol 2004; 44: 869-877. 11. Vasamreddy CR, Dalal D, Eldadah Z, Dickfeld T, Jayam VK, Henrickson C, Meininger G, Dong J, Lickfett L, Berger R, Calkins H. Safety and efficacy of circumferential pulmonary vein catheter ablation of atrial fibrillation. Heart Rhythm 2005; 2: 42-48. 12. Ouyang F, B nsch D, Ernst S, Schaumann A, Hachiya H, Chen M, Chun J, Falk P, Khanedani A, Antz M, Kuck KH. Complete isolation of left atrium surrounding the pulmonary veins: new insights from the doublelasso technique in paroxysmal atrial fibrillation. Circulation 2004; 110: 2090-2096. 13. Pak HN, Kim JS, Shin SY, Lee HS, Choi JI, Lim HE, Hwang C, Kim YH. Is Empirical Four Pulmonary Vein Isolation Necessary for Focally Triggered Paroxysmal Atrial Fibrillation? Comparison of Selective Pulmonary Vein Isolation Versus Empirical Four Pulmonary Vein Isolation. J Cardiovasc Electrophysiol 2008 Feb 12; [Epub ahead of print] 14. Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol 2004; 43: 2044-2053. 325

Kim YH 15. Oral H, Chugh A, Good E, Wimmer A, Dey S, Gadeela N, Sankaran S, Crawford T, Sarrazin JF, Kuhne M, Chalfoun N, Wells D, Frederick M, Fortino J, BenloucifMoore S, Jongnarangsin K, Pelosi F Jr, Bogun F, Morady F. Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex electrograms. Circulation 2007; 115: 2606-2612. 16. Scherlag BJ, Yamanashi WS, Schauerte P, Scherlag M, Sun YX, Hou Y, Jackman WM, Lazzara R. Endovascular stimulation within the left pulmonary artery to induce slowing of heart rate and paroxysmal atrial fibrillation. Cardiovasc Res 2002; 54: 470-475. 17. Oh S, Zhang Y, Bibevski S, Marrouche NF, Natale A, Mazgalev TN. Vagal denervation and atrial fibrillation inducibility: epicardial fat pad ablation does not have longterm effects. Heart Rhythm 2006; 3: 701-708. 18. Bertaglia E, Zoppo F, Tondo C, Colella A, Mantovan R, Senatore G, Bottoni N, Carreras G, Corò L, Turco P, Mantica M, Stabile G. Early complications of pulmonary vein catheter ablation for atrial fibrillation: a multicenter prospective registry on procedural safety. Heart Rhythm 2007; 4: 1265-1271. 19. Kim JH, Shin SY, Joo HJ, Hong SJ, Lim HE, Choi JI, Pak HN, Kim YH. Drugeluting stent for the therapy of pulmonary vein stenosis developed after catheter ablation of atrial fibrillation. Korean Circulation J 2008 (in press). 20. Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as firstline treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005; 293: 2634-2640. 21. Hsu LF, Ja l s P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M, Pasquie JL, Scave e C, Bordachar P, Cle menty J, Hal ssaguerre M. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004; 351: 2373-2383. Peer Reviewers Commentary 326